JP4282485B2 - 伸長グルカゴン様ペプチド−１アナログ - Google Patents
伸長グルカゴン様ペプチド−１アナログ Download PDFInfo
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- JP4282485B2 JP4282485B2 JP2003558463A JP2003558463A JP4282485B2 JP 4282485 B2 JP4282485 B2 JP 4282485B2 JP 2003558463 A JP2003558463 A JP 2003558463A JP 2003558463 A JP2003558463 A JP 2003558463A JP 4282485 B2 JP4282485 B2 JP 4282485B2
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- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Health & Medical Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Cardiology (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34647402P | 2002-01-08 | 2002-01-08 | |
| US40509702P | 2002-08-21 | 2002-08-21 | |
| PCT/US2003/000001 WO2003058203A2 (en) | 2002-01-08 | 2003-01-03 | Extended glucagon-like peptide-1 analogs |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005528337A JP2005528337A (ja) | 2005-09-22 |
| JP2005528337A5 JP2005528337A5 (https=) | 2006-02-02 |
| JP4282485B2 true JP4282485B2 (ja) | 2009-06-24 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003558463A Expired - Fee Related JP4282485B2 (ja) | 2002-01-08 | 2003-01-03 | 伸長グルカゴン様ペプチド−１アナログ |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US7482321B2 (https=) |
| EP (1) | EP1585959A4 (https=) |
| JP (1) | JP4282485B2 (https=) |
| AR (1) | AR038102A1 (https=) |
| AU (1) | AU2003200839B2 (https=) |
| BR (1) | BR0306706A (https=) |
| CA (1) | CA2468700A1 (https=) |
| MX (1) | MXPA04006679A (https=) |
| PE (1) | PE20030820A1 (https=) |
| TW (1) | TW200306202A (https=) |
| WO (1) | WO2003058203A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102363633A (zh) * | 2011-11-16 | 2012-02-29 | 天津拓飞生物科技有限公司 | 胰高血糖素样肽-1突变体多肽及其制备方法、药物组合物和其应用 |
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|---|---|---|---|---|
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| EP2298337B1 (en) | 2003-12-09 | 2017-02-22 | Novo Nordisk A/S | Regulation of food preference using GLP-1 agonists |
| AU2005203925A1 (en) | 2004-01-08 | 2005-07-21 | Theratechnologies Inc. | Glucagon-Like Peptide-1 analogs with long duration of action |
| EP1758575A1 (en) * | 2004-06-11 | 2007-03-07 | Novo Nordisk A/S | Counteracting drug-induced obesity using glp-1 agonists |
| EP1781692A2 (en) * | 2004-08-18 | 2007-05-09 | Eli Lilly And Company | Selective vpac2 receptor peptide agonists |
| CN100540565C (zh) | 2005-01-14 | 2009-09-16 | 无锡宏创医药科技有限公司 | 修饰的Exendins及其应用 |
| TWI362392B (en) | 2005-03-18 | 2012-04-21 | Novo Nordisk As | Acylated glp-1 compounds |
| US8603972B2 (en) | 2005-03-18 | 2013-12-10 | Novo Nordisk A/S | Extended GLP-1 compounds |
| WO2007017892A2 (en) * | 2005-05-05 | 2007-02-15 | Cadila Healthcare Limited | Novel compounds as glp-i agonists |
| CA2608311C (en) * | 2005-05-13 | 2012-11-27 | Eli Lilly And Company | Glp-1 pegylated compounds |
| WO2007021498A1 (en) * | 2005-08-11 | 2007-02-22 | Eli Lilly And Company | Selective vpac2 receptor peptide agonists |
| DE602005017628D1 (de) | 2005-09-22 | 2009-12-24 | Biocompatibles Uk Ltd | Fusionspolypeptide vom glp-1 (glucagon-like peptide-1) mit erhöhten peptidaseresistenz |
| CN101296708B (zh) | 2005-10-26 | 2011-12-07 | 伊莱利利公司 | 选择性vpac2受体肽激动剂 |
| US8202837B2 (en) * | 2005-11-04 | 2012-06-19 | Glaxosmithkline Llc | Methods for administering hypoglycemic agents |
| CA2913805A1 (en) | 2005-11-07 | 2007-05-18 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting physiological solubility and stability |
| EP2364735A3 (en) | 2005-12-16 | 2012-04-11 | Nektar Therapeutics | Branched PEG conjugates of GLP-1 |
| US20100048460A1 (en) * | 2006-02-28 | 2010-02-25 | Lianshan Zhang | Selective vpac2 receptor peptide agonists |
| JP2009532422A (ja) * | 2006-04-03 | 2009-09-10 | ノボ・ノルデイスク・エー／エス | Ｇｌｐ−１ペプチドアゴニスト |
| JP2009534423A (ja) | 2006-04-20 | 2009-09-24 | アムジェン インコーポレイテッド | Ｇｌｐ−１化合物 |
| EP1854455B1 (en) | 2006-05-10 | 2009-10-07 | Biocompatibles UK Limited | Spherical microcapsules comprising GLP-1 peptides, their production and use |
| TWI430806B (zh) * | 2006-09-13 | 2014-03-21 | Smithkline Beecham Corp | 用於投與長效降血糖藥劑之方法 |
| CA2677932A1 (en) | 2007-02-15 | 2008-08-21 | Indiana University Research And Technology Corporation | Glucagon/glp-1 receptor co-agonists |
| EP1972349A1 (en) * | 2007-03-21 | 2008-09-24 | Biocompatibles UK Limited | GLP-1 fusion peptides conjugated to polymer(s), their production and use |
| EP1975176A1 (en) * | 2007-03-27 | 2008-10-01 | Biocompatibles UK Limited | Novel glp-1 fusion peptides, their production and use |
| US20110034373A1 (en) * | 2007-08-03 | 2011-02-10 | Eli Lilly And Company | Use of an fgf-21 compound and a glp-1 compound for the treatment of obesity |
| MX2010004298A (es) | 2007-10-30 | 2010-05-03 | Univ Indiana Res & Tech Corp | Compuestos que exhiben actividad antagonista de glucagon y agonista de glp-1. |
| US8450270B2 (en) * | 2008-06-17 | 2013-05-28 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting enhanced solubility and stability in physiological pH buffers |
| CN102105159B (zh) | 2008-06-17 | 2015-07-08 | 印第安纳大学研究及科技有限公司 | 基于gip的混合激动剂用于治疗代谢紊乱和肥胖症 |
| US8889618B2 (en) | 2008-11-07 | 2014-11-18 | The General Hospital Corporation | C-terminal fragments of glucagon-like peptide-1 (GLP-1) |
| PT2373681T (pt) | 2008-12-10 | 2017-04-11 | Glaxosmithkline Llc | Composições farmacêuticas de albiglutida |
| PE20120332A1 (es) | 2008-12-19 | 2012-04-14 | Univ Indiana Res & Tech Corp | Profarmacos de peptido de la superfamilia de glucagon basado en amida |
| EP2443146B1 (en) | 2009-06-16 | 2016-10-05 | Indiana University Research And Technology Corporation | Gip receptor-active glucagon compounds |
| KR20120123443A (ko) | 2010-01-27 | 2012-11-08 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 대사 장애 및 비만 치료용 글루카곤 길항제-ｇｉｐ 항진제 콘쥬게이트 |
| US8691763B2 (en) | 2010-05-04 | 2014-04-08 | Glaxosmithkline Llc | Methods for treating or preventing cardiovascular disorders and providing cardiovascular protection |
| MX2012013001A (es) | 2010-05-13 | 2013-02-26 | Univ Indiana Res & Tech Corp | Peptidos de la superfamilia de glucagon que presentan actividad del receptor nuclear de hormonas. |
| JP6050746B2 (ja) | 2010-05-13 | 2016-12-21 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションIndiana University Research And Technology Corporation | Ｇタンパク質共役受容体活性を示すグルカゴンスーパーファミリーのペプチド |
| EP2588126A4 (en) | 2010-06-24 | 2015-07-08 | Univ Indiana Res & Tech Corp | AMID-BASED GLUCAGON SUPERFAMILY PEPTIDE PRODRUGS |
| WO2012054822A1 (en) | 2010-10-22 | 2012-04-26 | Nektar Therapeutics | Pharmacologically active polymer-glp-1 conjugates |
| WO2012054861A1 (en) | 2010-10-22 | 2012-04-26 | Nektar Therapeutics | Glp-1 polymer conjugates having a releasable linkage |
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| US8507428B2 (en) | 2010-12-22 | 2013-08-13 | Indiana University Research And Technology Corporation | Glucagon analogs exhibiting GIP receptor activity |
| RS56173B1 (sr) | 2011-06-22 | 2017-11-30 | Univ Indiana Res & Tech Corp | Koagonisti receptora za glukagon/glp-1 receptora |
| KR20140043793A (ko) | 2011-06-22 | 2014-04-10 | 인디애나 유니버시티 리서치 앤드 테크놀로지 코퍼레이션 | 글루카곤/glp-1 수용체 공동-작용물질 |
| WO2013006692A2 (en) * | 2011-07-06 | 2013-01-10 | The General Hospital Corporation | Methods of treatment using a pentapeptide derived from the c-terminus of glucagon-like peptide 1 (glp-1) |
| JP6324315B2 (ja) | 2011-11-17 | 2018-05-16 | インディアナ ユニバーシティー リサーチ アンド テクノロジー コーポレーションＩｎｄｉａｎａ Ｕｎｉｖｅｒｓｉｔｙ Ｒｅｓｅａｒｃｈ Ａｎｄ Ｔｅｃｈｎｏｌｏｇｙ Ｃｏｒｐｏｒａｔｉｏｎ | グルココルチコイド受容体の活性を示すグルカゴンスーパーファミリーのペプチド |
| EP2782590A4 (en) | 2011-11-23 | 2016-08-03 | Durect Corp | BIODEGRADABLE AND MEDIUM-RADIATED STERILIZED MEDICAMENTAL COMPOSITIONS |
| CN104583232B (zh) | 2012-06-21 | 2018-04-13 | 印第安纳大学研究及科技有限公司 | 展现gip受体活性的胰高血糖素类似物 |
| JP6475233B2 (ja) * | 2013-06-20 | 2019-02-27 | ノヴォ ノルディスク アー／エス | Ｇｌｐ−１誘導体及びその使用 |
| US10626156B2 (en) | 2013-12-06 | 2020-04-21 | Jie Han | Bioreversable promoieties for nitrogen-containing and hydroxyl-containing drugs |
| EP3079668A1 (en) | 2013-12-09 | 2016-10-19 | Durect Corporation | Pharmaceutically active agent complexes, polymer complexes, and compositions and methods involving the same |
| JP6730278B2 (ja) | 2014-11-27 | 2020-07-29 | ノヴォ ノルディスク アー／エス | Ｇｌｐ−１誘導体及びその使用 |
| WO2016097108A1 (en) | 2014-12-17 | 2016-06-23 | Novo Nordisk A/S | Glp-1 derivatives and uses thereof |
| MX2020010505A (es) | 2018-04-05 | 2021-01-15 | Sun Pharmaceutical Ind Ltd | Analogos novedosos de glp-1. |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL128332A0 (en) * | 1996-08-30 | 2000-01-31 | Novo Nordisk As | GLP-1 derivatives |
| WO1999043706A1 (en) * | 1998-02-27 | 1999-09-02 | Novo Nordisk A/S | Derivatives of glp-1 analogs |
| JP2002506792A (ja) | 1998-02-27 | 2002-03-05 | ノボ ノルディスク アクティーゼルスカブ | Ｎ末端修飾ｇｌｐ−１誘導体 |
| ATE251465T1 (de) | 1998-07-31 | 2003-10-15 | Novo Nordisk As | In-vitro stimulation von beta zellen vermehrung |
| IL155812A0 (en) * | 2000-12-07 | 2003-12-23 | Lilly Co Eli | Glp-1 fusion proteins |
| ATE408414T1 (de) | 2001-07-31 | 2008-10-15 | Us Gov Health & Human Serv | Glp 1 exendin 4 peptidanaloga und deren verwendungen |
| EP1432430A4 (en) * | 2001-08-28 | 2006-05-10 | Lilly Co Eli | PREMIXTURES OF GLP-1 AND BASALINSULIN |
| MXPA04003569A (es) * | 2001-10-19 | 2004-07-23 | Lilly Co Eli | Mezclas bifasicas de glp-1 e insulina. |
-
2003
- 2003-01-03 AU AU2003200839A patent/AU2003200839B2/en not_active Ceased
- 2003-01-03 JP JP2003558463A patent/JP4282485B2/ja not_active Expired - Fee Related
- 2003-01-03 WO PCT/US2003/000001 patent/WO2003058203A2/en not_active Ceased
- 2003-01-03 TW TW092100093A patent/TW200306202A/zh unknown
- 2003-01-03 CA CA002468700A patent/CA2468700A1/en not_active Abandoned
- 2003-01-03 MX MXPA04006679A patent/MXPA04006679A/es unknown
- 2003-01-03 BR BRPI0306706-8A patent/BR0306706A/pt not_active IP Right Cessation
- 2003-01-03 EP EP03700026A patent/EP1585959A4/en not_active Withdrawn
- 2003-01-03 AR ARP030100014A patent/AR038102A1/es unknown
- 2003-01-03 US US10/499,111 patent/US7482321B2/en not_active Expired - Fee Related
- 2003-01-06 PE PE2003000021A patent/PE20030820A1/es not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102363633A (zh) * | 2011-11-16 | 2012-02-29 | 天津拓飞生物科技有限公司 | 胰高血糖素样肽-1突变体多肽及其制备方法、药物组合物和其应用 |
| CN102363633B (zh) * | 2011-11-16 | 2013-11-20 | 天津拓飞生物科技有限公司 | 胰高血糖素样肽-1突变体多肽及其制备方法、药物组合物和其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| PE20030820A1 (es) | 2003-10-04 |
| AU2003200839A1 (en) | 2003-07-24 |
| AU2003200839B2 (en) | 2008-12-11 |
| AR038102A1 (es) | 2004-12-29 |
| US7482321B2 (en) | 2009-01-27 |
| BR0306706A (pt) | 2007-03-27 |
| WO2003058203A2 (en) | 2003-07-17 |
| TW200306202A (en) | 2003-11-16 |
| MXPA04006679A (es) | 2004-11-10 |
| CA2468700A1 (en) | 2003-07-17 |
| US20060014241A1 (en) | 2006-01-19 |
| EP1585959A2 (en) | 2005-10-19 |
| EP1585959A4 (en) | 2007-11-14 |
| JP2005528337A (ja) | 2005-09-22 |
| WO2003058203A3 (en) | 2007-02-01 |
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